Method and composition for preventing and treating viral infections

ABSTRACT

A method and composition for treating viral infections using a combination of naturally occurring compounds is provided. The method includes administering to a patient at risk of or diagnosed with a viral infection a composition including therapeutically effective amounts of a helicase ATPase inhibitor, a sialidase enzyme inhibitor, an ICAM-1 inhibitor and gallic acid which each also down regulate the immune response. The composition may further include a permeation enhancer.

FIELD OF THE INVENTION

The present disclosure relates generally to limiting the occurrence ofand/or treating viral infections, and more particularly to a therapeuticmethod and a therapeutic composition having a helicase ATPase inhibitor,a sialidase enzyme inhibitor, an ICAM-1 inhibitor and gallic acid,advantageously administered to a patient at risk of, or diagnosed with,a viral infection.

BACKGROUND OF THE INVENTION

Many human diseases result from infection by microscopic organismscalled viruses. Infection by viruses can give rise to symptoms that varyfrom mild to severe. Viral infections can result in large numbers ofdeaths. Examples of such pandemics include the Spanish flu of 1918-1919that killed approximately 40 million people and the HIV/AIDS epidemicthat has killed almost 2 million people.

Viruses require host organisms in order to replicate and viruses aretransmitted from an infected host to an uninfected host through a numberof mechanisms. A virus will first attach itself to a host cell. It willthen enter the cell and release its genetic code (i.e., RNA or DNA). Thevirus makes use of the host cell's functional proteins and enzymes inorder to replicate. Eventually, the host cell may die because themechanisms it needs to survive are controlled by the virus. After deathof the cell, the replicated viruses are released, allowing them toattack new host cells and continuing the replication process. Someviruses cause modification of the host cells leading to cancer, whileother viruses can remain dormant in the host for an extended periodprior to the infection becoming symptomatic in the host.

The symptoms that result from viral infections can vary fromvirus-to-virus as any one virus typically will infect only certain typesof cells. This observation also means that a specific virus willtypically infect only certain species, although mutation of a virus canallow it to extend the number of species that any one virus is able toinfect.

Host species have developed a number of defense mechanisms to protectthemselves from viral infections. The first lines of defense aremechanisms that prevent viral entry into the host. The skin provides animpermeable barrier to entry. Viruses typically enter the body throughbody cavities and can pass through the mucosal surfaces that line thesecavities. Once a virus is in the body and detected by the body's immunesystem, lymphocytes and monocytes in the blood learn how to attack theinvader. Invaded cells release cytokines such as the interferons (forexample IL 1, IL 6, IL 12, IL 16), tumor necrosis factor (TNF-a), andinterferons (typically interferons a and g). The role of these cytokinesis to increase the resistance of other host cells to the invading virus.Many of the symptoms of viral infection experienced by the host resultsfrom the extensive release of cytokines, commonly referred to as thecytokine storm.

The white blood cells are able to remember how to combat viruses thathave previously invaded the body. So if the host survives the initialattack of the virus, the immune system is able to respond much morequickly to subsequent infections of the same virus. The body hasdeveloped an immunity to the virus. Such immunity can also be induced bypresenting the immune system with a surrogate (vaccine) for the virus ina process known as immunization.

Antiviral drugs are known in the art to assist the immune system inovercoming a viral infection in a patient. Most antiviral drugs work byslowing the replication of the virus in the infected patient's body thusallowing the body's immune system to launch an effective response whenthe disease symptoms are less severe. Antiviral drugs may workspecifically on one or two viruses or may be effective across a broadspectrum of viruses. There are many known mechanisms by which antiviralagents can slow viral replication. One antiviral strategy is to slow orprevent the virus infiltrating a target cell, for example by binding toa receptor on the target cell which is required by the virus to enterthe cell or by coating the virus so preventing its ability to bind tothe target receptor(s). Other antiviral agents can slow viralreplication once the virus particle has entered the target cell. Suchmechanisms are well known in the art.

SUMMARY OF THE INVENTION

The present invention relates to a method and composition for treatingviral infections using a combination of naturally occurring compounds.In one embodiment, the method includes administering to a patient atrisk of or diagnosed with a viral infection a composition includingtherapeutically effective amounts of a helicase ATPase inhibitor, asialidase enzyme inhibitor an ICAM-1 inhibitor and gallic acid. Thecomposition may further include a permeation enhancer.

The composition is effective in combating a viral infection by reducingreplication rates for the virus and by reducing the virus's ability tostimulate the immune response of the host, thereby preserving cellularintegrity. Specifically, the composition is effective in inhibiting theATPase activity of the replication enzyme helicase on the cell surfaceby docking site competition. Moreover, the composition is effective ininhibiting the sialidase and ICAM-1 enzymes, which are involved in theentry and release stages of intercellular virus particles. Although notwishing to be limited to one function, it is believed that gallic acidwill function as an inflammation and pain inhibitor, e.g. targetingTNF-a and nociceptors, respectively.

In one aspect of the invention there is provided a method of preventingand treating viral infections including administering a includingtherapeutically effective amounts of a helicase ATPase inhibitor, asialidase composition enzyme inhibitor, an ICAM-1 inhibitor and gallicacid to a patient at risk of or diagnosed with a viral infection.

In another aspect of the invention there is provided a composition fortreating viral infections including therapeutically effective amounts ofa helicase ATPase inhibitor, a sialidase enzyme inhibitor, an ICAM-1inhibitor and gallic acid.

In one embodiment, the composition is administered to the patient byoral administration, intravenous injection, intramuscular injection,intrathecal injection, subcutaneous administration, sublingually, buccaladministration, rectal administration, vaginal administration, ocularadministration, otic administration, nasal administration, inhalationthrough the mouth, inhalation through the nose, transdermally or anycombination thereof.

In another embodiment, the helicase ATPase inhibitor includes anaturally occurring compound, a synthetic derivative of a naturallyoccurring compound or a combination thereof.

In another embodiment, the naturally occurring ATPase inhibitor compoundincludes a flavonoid, a flavonoid derivative or a combination thereof.

In another embodiment, the flavonoid ATPase inhibitor is myricetin.

In another embodiment, the I-CAM 1 inhibitor includes a flavonoid, aflavonoid derivative or a combination thereof.

In another embodiment, the ICAM-1 inhibitor is myricetin.

In another embodiment, the sialidase enzyme inhibitor includes anaturally occurring compound, a synthetic derivative of a naturallyoccurring compound or a combination thereof.

In another embodiment, the naturally occurring sialidase enzymeinhibitor compound includes a flavonoid, a flavonoid derivative or acombination thereof.

In another embodiment, the flavonoid sialidase enzyme inhibitor ishesperitin or hesperidin.

In another embodiment, the viral infection is the Ebola virus.

In another embodiment, the patient is a human.

In another embodiment, the composition further includes a permeationenhancer.

In another embodiment, the permeation enhancer is piperine.

In another embodiment, the helicase ATPase and ICAM-1 inhibitor ismyricetin and the sialidase enzyme inhibitor is hesperitin.

In another embodiment, the composition further includes piperine.

In another embodiment, about 300 to about 700 mg myricetin; about 100 toabout 500 mg hesperitin; about 5 to about 100 mg piperine and about 150mg-300 mg gallic acid are present in the composition.

In another embodiment, about 450 to about 600 mg myricetin; about 250 toabout 400 mg hesperitin; about 5 to about 50 mg piperine; and about250-450 mg gallic acid are present in the composition.

In another embodiment, about 55 to about 75% weight myricetin; about 30to about 50% hesperitin; about 0.5 to about 5% piperine; and about 10%to 25% gallic acid, based on the total weight of the mixture, is presentin the composition.

In another embodiment, the ratio of piperine, myricetin, hesperitin andgallic acid present in the composition is about 1:(30-60):(30-60):30-60.

In another aspect of the invention there is provided a method ofpreventing and treating the Ebola virus in a human includingadministering a composition including 40% myricetin, 30% hesperitin, 1%piperine and 29% gallic acid, based on the total weight of the mixture,to a human at risk of or diagnosed with a the Ebola virus.

In another aspect of the invention there is provided a composition forpreventing and treating the Ebola virus including 60% myricetin, 39%hesperitin and 1% piperine, based on the total weight of the mixture.

DETAILED DESCRIPTION

As used herein, the following terms and phrases shall have the meaningset forth below.

The phrase “naturally occurring” when referring to a compound means acompound that is in a form in which it can be found naturally. Acompound is not in a form that is naturally occurring if, for example,the compound has been purified and separated from at least some of theother molecules that are found with the compound in nature. A “naturallyoccurring compound” refers to a compound that can be found in nature,i.e., a compound that has not been created or modified by man.

“Treating” a condition or disease refers to curing as well asameliorating at least one symptom of the condition or disease.

The term “therapeutic effect” is art-recognized and refers to a local orsystemic effect in animals, particularly mammals, and more particularlyhumans caused by a pharmacologically active substance. The phrase“therapeutically effective amount” means that amount of such a substancethat produces some desired local or systemic effect at a reasonablebenefit/risk ratio applicable to any treatment. The therapeuticallyeffective amount of such substance will vary depending upon the patientand disease or condition being treated, the weight and age of thepatient, the severity of the disease or condition, the manner ofadministration and the like, which can readily be determined by one orordinary skill in the art. For example, certain compositions describedherein may be administered in a sufficient amount to produce a desiredeffect at a reasonable benefit/risk ratio applicable to such treatment.

The term “pharmaceutically acceptable carrier” means a carrier ordiluent that does not give a stimulus to an organism and destroy thenatures and bioactivities of an administered compound.

The present invention is directed to administering a compositioncomprising therapeutically effective amounts of a helicase ATPaseinhibitor, a sialidase enzyme inhibitor, an ICAM-1 inhibitor, and gallicacid to a patient at risk of or diagnosed with a viral infection.

In one embodiment, the effective concentration for a compositionconsisting of a mixture by weight of a helicase ATPase inhibitor, asialidase enzyme inhibitor, an ICAM-1 inhibitor and gallic acid, rangesfrom about 250 mg to about 1000 mg of the composition. In oneembodiment, a single dose per day, taken at the beginning of the day, isabout 750 mg, or about 1500 mg. In another embodiment, the compositionis administered as a dose three times a day in an amount of about 750 mgper dose. The total amount of the composition administered daily, in oneembodiment is at least 500 mg, or at least 750 mg, or at least 1000 mgor at least 2500 mg.

The helicase ATPase inhibitor of the present invention functions as acellular replication inhibitor by inhibiting the ATPase activity of thereplication enzyme helicase on the cell surface by docking sitecompetition. This inhibition reduces viral un-packaging and replicationrates and reduces mutation of viral strain due to the inhibitingactivity taking place outside the cell.

In one embodiment, the helicase ATPase inhibitor includes a naturallyoccurring compound, a synthetic derivative of a naturally occurringcompound or a combination thereof. There are several naturally occurringcompounds that have an effect on viral infections.

In one embodiment, the naturally occurring ATPase inhibitor compoundcomprises a flavonoid, a flavonoid derivative or a combination thereof.Flavonoids are naturally-occurring antioxidant compounds for whichseveral therapeutic uses have been demonstrated including diabetes,neurological disorders, thrombin inhibition, cancer, and antivirals.Generally, flavonoids generate few side-effects when administered andcan safely be provided to patients in large doses. Two types offlavonoids that are useful are flavanones and flavones. Flavanones havethe structure (I) shown below and flavones have the similar structure(II) shown below:

wherein R, R₁, R₂, R₃, R₄, R₅ and R₆ are each independently hydrogen, ahydroxy group, an alkoxy group, a rutinosyl group, a rhamnosyl group, asubstituted alkoxy group or a substituted acyloxy group wherein thesubstituent is chosen from hydroxyl, alkoxy, aryloxy, phenyl, halogen,and amido group. Several examples of the flavonoids of formula (I) and(II) are shown below in Table 1.

TABLE 1 R R₁ R₂ R₃ R₄ R₅ R₆ FLAVONE Flavone H H H H H H H Chrysin OH OHH H H H H Apigenin OH OH H H H OH H Luteolin OH OH H H H OH H Diosmin-0- OH H H OH OCH₃ H rutinose Fisetin OH H OH H OH OH H Kaempferol OH OHOH H H OH H Morin OH OH OH OH H OH H Quercetin OH OH OH H OH OH HMyricetin OH OH OH H OH OH OH Rutin OH OH -0- H OH OH H rutinoseRhoifolin R-G-^(a) OH H H H OH H FLAVANONE Galangin OH OH OH H H H HHesperetin OH OH H H OH OCH₃ H Eriodictyol OH OH H H OH OH H NaringeninOH OH H H H OH H Naringin R-G-^(a) OH H H H OH H Neohesperidin R-G-^(b)OH H H OH OCH₃ H Hesperidin R-G-^(b) OH H H OH OCH₃ H Narirutin R-G-^(b)OH H H H OH H Prunin Glu- OH H H H OH H cose- ^(a)rhamnose-glucose,L-rhamnose is linked α 1−>2 to D-glucose ^(b)rhamnose- glucose,L-rhamnose is linked α 1−>6 to D-glucose

In one embodiment, the helicase ATPase inhibitor is the flavonoidmyricetin.

Myricetin is a flavonoid found in most berries, including cherry,cranberry and bilberry, and other plants, including parsley andrutabagas. In addition to inhibiting the enzyme helicase, myricetinfunctions as a powerful and broad cytokine signaling inhibitor andimmune-modulator. Myricetin down-regulates cytokine activity and TNF-A.This includes, for example, lymphokines, interleukines and chemokines,particularly interleukins IL-IL-36 and TNF-A.

Naturally occurring flavonoids, such as myricetin, are commonlysubstituted at variable positions, mainly by hydroxyl, methoxyl,isoprenyl and glycosyl groups. The introduction of halogens in thesemolecules show strong biological activities, including antiviralproperties.

The ICAM-1 inhibitor of the present invention functions to slow viralreplication inside the cell by inhibiting the ICAM-1 enzyme, which isinvolved in entry and release stages of intercellular virus particles.

In one embodiment, the ICAM-1 inhibitor is the flavonoid myricetin.

The sialidase of the present invention functions to slow viralreplication inside the cell by inhibiting the sialidase enzyme, which isinvolved in entry and release stages of intercellular virus particles.

In one embodiment, the sialidase enzyme inhibitor comprises a naturallyoccurring compound, a synthetic derivative of a naturally occurringcompound or a combination thereof. In another embodiment, the naturallyoccurring sialidase enzyme inhibitor compound comprises a flavonoid, aflavonoid derivative or a combination thereof.

In one embodiment, the sialidase enzyme inhibitor is the flavonoidhesperitin or hesperidin. Hesperidin is a flavonoid found in plants,mainly in citrus fruit peels.

Hesperitin is the aglycone form of hesperidin. In addition to inhibitingthe sialidase enzyme, hesperitin and hesperidin function as cellularintegrity agents by inhibiting cellular stratum acidification due toexcessive histamine and histadine concentrations. Hesperitin andhesperidin further prevent integrin loss by inhibition of intracellularH₂O₂ production as well as activation of nuclear factor kB,phosphorylation of IkB (alpha), and inhibition of P-38 MAPK (mitogenactivated kinase). Hesperitin and hesperidin further enhance cellularintegrity by stimulating fibroblast collagen synthesis with associatedenhancement of migration and proliferation.

There are several methods by which myricetin, hesperitin or hesperidinmay be harvested from their original botanical sources. In one method,for example, extraction from botanical sources begins with a suitableseed material such as grape seeds or tomato seeds, pine bark or citrusrinds. The source material is macerated and flushed with water toseparate the water soluble flavonoids from the bulkier pectins andfibers of the source material. This pulp wash is then treated withappropriate acids and bases as known in the art to cause precipitation.The precipitate is then washed again, dried and then concentrated toyield a fairly pure flavonoid composition. This composition may befurther clarified to yield fractions containing the desired flavonoidproduct.

In another method, reverse osmosis may be used to remove the targetflavonoid by filtering it out of juice streams from beveragemanufacturing processes. The process of manufacturing fruit juices suchas citrus, liberates the flavonoids from the rind and suspends them inthe juice product. It is often desirable to remove these water solubleflavonoids because of their tendency to produce bitter or off flavors inthe juice product.

For example, during the manufacture of grapefruit juice, the primarygrapefruit flavonoid naringin is released into the juice stream. Becausenaringin has a very distinct bitter taste, it is necessary to remove itfrom the product stream via the use of resin coated reverse osmosisdevices to restore the proper flavor profile of the grapefruit juice.The resultant flavonoid is finally collected and dried to yield a fairlypure product.

The flavonoids may also be manufactured by synthetic methods. Suchmethods may include an Allan-Robinson Reaction, which is a chemicalreaction of o-hydroxylaryl ketones with aromatic anhydrides to formflavanones. Another example is Auwers Synthesis, which is a procedurethat requires an acid catalyzed aldol condensation between benzaldehydeand a 3-oxypentanon to an o-hydroxychalcone. Further bromination of thealkene group gives a dibromo-adduct that rearranges to a flavanol byreaction with potassium hydroxide. A further example is aBaker-Venkataraman Rearrangement, which involves the reaction of2-acetoxyacetophenones with base to form 1,3-diketones. Therearrangement reaction proceeds via enolate formation followed by anacyl transfer to form flavanones. An Algar-Flynn-Oyamada Reaction mayalso be used. In this reaction, a chalcone undergoes an oxidativecyclization to form a flavanol.

The present invention prevents and treats a wide variety of virusinfections including, but not limited, to Cowpoxvirus, Herpesviridae,Herpes simplex viruses, Epstein-Barr virus, human adenoviruses, humanpapillomaviruses, hepatitis B virus, Retroviridae (such as humanimmunodeficiency virus), rotavirus, Filoviridae (such as Marburg virusand Ebola viruses), Dengue virus, influenza viruses, hanta virus, Severeacute respiratory syndrome coronavirus, Entero viruses, Rhino virus,Hepatitis virus, Norovirus, Norwalk virus, Alpha viruses, Chikungunyavirus, Venezuelan equine encephalitis virus, Western equine encephalitisvirus, Eastern equine encephalitis virus, St. Louis encephalitis virus,West Nile virus, Yellow fever virus, and Creutzfeldt-Jakob-Disease,Arbovirus, Flavivirus and RNA viruses.

In one embodiment, the viral infection is the Ebola virus. Viral Ebola'slethality is caused by the virus's ability to over stimulate the host'sautoimmune response. The resulting saturation of the host's cytokinechemicals causes rapid cell adhesion loss due to the cytokine'sdestabilizing activity on integrin. The result is loss in cellularintegrity and finally fatal hemorrhaging of vascular tissues and organs.

Ebola accomplishes this by secreting specific glycol-proteins (e.g.,secreted glyol-protein (sGP)) that interact with specific receptors onthe cell surface to stimulate immune signaling response. Theover-signaling initiates a cytokine response, which in turn initiateschemokine release. The resulting and overwhelming concentration ofchemokines leads to integrin loss at the cellular level.

The present invention combats the Ebola virus by reducing replicationrates for the virus and reducing the virus's ability to stimulate theimmune response of the host, thereby preserving cellular integrity.

The composition of the present invention may be administered to patientsat risk of viral infection, for example through exposure to patientsknown or suspected of having a viral disease, in order to prevent orlessen the severity of symptoms following infection and/or reduce thepossibility of severe symptoms or death following infections.

The composition of the present invention may be administered to patientsknown or suspected of having a viral disease, in order to lessen theseverity of symptoms and/or reduce the possibility of severe symptoms ordeath.

In one embodiment, the patient is a human. In other embodiments, thepatient may be a mammal other than a human, such as a dog.

In one embodiment, the composition further includes a permeationenhancer. The permeation enhancer of the present invention functions toenhance oral uptake or cellular uptake of the helicase ATPase inhibitor,ICAM-1 enzyme inhibitor and the sialidase enzyme inhibitor.

In one embodiment, the permeation enhancer is piperine. Piperine is analkaloid and is responsible for the pungency of black pepper and longpepper. Piperine is commercially available or may be extracted fromblack pepper using dichloromethane. Piperine increases thebioavailability of nutrients.

In one embodiment, the helicase ATPase inhibitor and ICAM-1 inhibitor ismyricetin, the sialidase enzyme inhibitor is hesperitin and thecomposition further includes piperine and gallic acid.

In one embodiment, the composition includes about 300 to about 700 mgmyricetin; about 100 to about 500 mg hesperitin; and about 5 to about100 mg piperine. In another embodiment, the composition includes about450 to about 600 mg myricetin; about 250 to about 400 mg hesperitin;about 5 to about 50 mg piperine, and about 100 to about 300 mg gallicacid.

In one embodiment, the composition includes a mixture of about 50 toabout 80% weight myricetin; about 25 to about 55% hesperitin; about 0.5to about 10% piperine; and about 10-30% gallic acid based on the totalweight of the mixture. In another embodiment, the composition includes amixture of about 55 to about 75% weight myricetin; about 30 to about 50%hesperitin; about 0.5 to about 5% piperine, and about 20-40% gallic acidbased on the total weight of the mixture. In yet another embodiment, thecomposition includes a mixture of about 40% myricetin; about 30%hesperitin; 1% piperine, and 29% gallic acid based on the total weightof the mixture.

In one embodiment, the composition includes a ratio of piperine tomyricetin to hesperitin of about 1:(2-4):(2-4), or about 1:(2-3):(2-3),or about 1:3:3. In another embodiment, the composition includes a ratioof piperine to myricetin to hesperitin to gallic acid of about1:(20-75):(20-75):(20-75), or about 1:(30-60):(30-60):(30-60), or about1:(40-55):(40-55).

In one embodiment, the composition is administered to the patient byoral administration, intravenous injection, intramuscular injection,intrathecal injection, subcutaneous administration, sublingually, buccaladministration, rectal administration, vaginal administration, ocularadministration, otic administration, nasal administration, inhalationthrough the mouth, inhalation through the nose, transdermally or anycombination thereof.

Formulations of the invention suitable for oral administration may be inthe form of capsules, cachets, pills, tablets, lozenges, powders,granules, or as a solution or a suspension in an aqueous or non-aqueousliquid, or as an oil-in-water or water-in-oil liquid emulsion, or as anelixir or syrup, each containing a predetermined amount of a compound ofthe present invention as an active ingredient.

In solid dosage forms of the invention for oral administration, theactive ingredient is mixed with one or more pharmaceutically-acceptablecarriers, such as sodium citrate or dicalcium phosphate, and/or any ofthe following: (1) fillers or extenders, such as starches, lactose,sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as,for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol;(4) disintegrating agents, such as agar-agar, calcium carbonate, potatoor tapioca starch, alginic acid, certain silicates, and sodiumcarbonate; (5) solution retarding agents, such as paraffin; (6)absorption accelerators, such as quaternary ammonium compounds; (7)wetting agents, such as, for example, cetyl alcohol and glycerolmonostearate; (8) absorbents, such as kaolin and bentonite clay; (9)lubricants, such a talc, calcium stearate, magnesium stearate, solidpolyethylene glycols, sodium lauryl sulfate, and mixtures thereof and(10) coloring agents. In the case of capsules, tablets and pills, thepharmaceutical compositions may also comprise buffering agents.

Embodiments of inventive compositions and methods are illustrated in thefollowing examples. These examples are provided for illustrativepurposes and are not considered limitations on the scope of inventivecompositions and methods.

EXAMPLES Example 1

A gelatin capsule containing 300 mg myricetin, 195 mg hesperitin, 5 mgpiperine and 200 mg gallic acid is administered orally to a patienttwice a day, taken with food.

Example 2

A tablet containing sodium citrate, 500 mg myricetin, 300 mg hesperitin,10 mg piperine and 300 mg gallic acid is administered orally once a dayupon rising.

Example 3

A powder containing 600 mg myricetin, 390 mg hesperitin, 10 mg piperineand 200 mg gallic acid is sprinkled onto foods such as, for examplescrambled eggs after cooking but prior to consumption.

Example 4

A composition containing a blend of 50% by weight myricetin, 25% byweight hesperitin, 10% by weight piperine and 15% gallic acid is blendedinto a saline solution and is injected intravenously, such that there is1 mg of the composition per 1 g of saline solution.

For the purposes of promoting an understanding of the principles of theinvention, the invention has been explained in relation to variousembodiments, it is to be understood that various modifications thereofwill be apparent to those skilled in the art upon reading thespecification. The features of the various embodiments of the articlesdescribed herein may be combined within an article. Therefore, it is tobe understood that the invention described herein is intended to coversuch modifications as fall within the scope of the appended claims.

The invention claimed is:
 1. A method of limiting the occurrence of ortreating viral infections comprising administering a compositioncomprising a mixture comprising therapeutically effective amounts ofmyricetin, hesperitin and gallic acid, to a patient at risk of ordiagnosed with a viral infection, to thereby limit the occurrence ortreat the viral infection.
 2. The method of claim 1, wherein influenzais the viral infection.
 3. The method of claim 1, wherein thecomposition is administered to the patient by oral administration,intravenous injection, intramuscular injection, intrathecal injection,subcutaneous administration, sublingually, buccal administration, rectaladministration, vaginal administration, ocular administration, oticadministration, nasal administration, inhalation through the mouth,inhalation through the nose, transdermally or any combination thereof.4. The method according to claim 1, wherein the viral infection is theEbola virus.
 5. The method according to claim 1, wherein the patient isa human.
 6. The method according to claim 1, wherein the mixture furthercomprises a permeation enhancer.
 7. The method of claim 6, wherein thepermeation enhancer is piperine.
 8. The method of claim 7, wherein about300 to about 700 mg myricetin; about 100 to about 500 mg hesperitin; andabout 5 to about 100 mg piperine are present in the composition.
 9. Themethod of claim 7, wherein about 450 to about 600 mg myricetin; about250 to about 400 mg hesperitin; and about 5 to about 50 mg piperine arepresent in the composition.
 10. The method of claim 7, wherein about 55to about 75% weight myricetin; about 30 to about 50% hesperitin; andabout 0.5 to about 5% piperine, based on the total weight of themixture, is present in the composition.
 11. The method of claim 7,wherein the molar ratio of piperine, myricetin and hesperitin present inthe composition is about 1:(30-60):(30-60).
 12. A method of limiting theoccurrence of or treating the Ebola virus in a human comprisingadministering a composition comprising a mixture of 40% myricetin, 30%hesperitin, 1% piperine, and 29% gallic acid, based on the total weightof the mixture, to a human at risk of or diagnosed with the Ebola virus.13. A composition for treating viral infections comprising a mixturecomprising therapeutically effective amounts of myricetin, hesperitinand gallic acid, at a molar ratio of 1:1:1.
 14. The compositionaccording to claim 13, wherein the mixture further comprises apermeation enhancer.
 15. The composition of claim 14, wherein thepermeation enhancer is piperine.
 16. The composition of claim 15,wherein about 5 to about 100 mg piperine are present in the composition.17. The composition of claim 15, wherein about 5 to about 50 mg piperineare present in the composition.
 18. The composition of claim 15, whereinabout 0.5 to about 5% piperine, based on the total weight of themixture, is present in the composition.
 19. The composition of claim 18,wherein based on a total weight of the mixture, the compositioncomprises 1% piperine.
 20. The composition of claim 15, wherein themolar ratio of piperine, myricetin and hesperitin present in thecomposition is about 1:(30-60):(30-60).